Singh Ajeet, Irfan Hamza, Fatima Eeshal, Nazir Zainab, Verma Amogh, Akilimali Aymar
Department of Internal Medicine, Dow University of Health Sciences, Karachi.
Department of Medicine, Shaikh Khalifa Bin Zayed Al Nahyan Medical and Dental College Lahore.
Ann Med Surg (Lond). 2024 May 15;86(8):4555-4559. doi: 10.1097/MS9.0000000000002146. eCollection 2024 Aug.
Sickle cell disease (SCD) is a hereditary hemoglobinopathy resulting from a β-globin chain mutation that causes abnormal hemoglobin (HbS) polymerization and leads to severe complications. Current treatment options primarily focus on symptom management, with limited curative potential. Recently, Casgevy, the first CRISPR/Cas9-based gene therapy for SCD, has received breakthrough FDA approval. Clinical trials have shown that Casgevy administered to patients aged older than or equal to 12 years enables precise modifications in hematopoietic stem cells, resulting in elevated fetal hemoglobin (HbF) levels and a significant reduction in vaso-occlusive events. Unlike conventional treatments, this therapy offers a curative approach and eliminates the need for recurrent transfusions and transplants, thereby improving the quality of life of patients with SCD. Casgevy has emerged as a beacon of hope for SCD patients and signifies a potential paradigm shift in SCD management due to its safety, curative potential, and transformative impact, positioning it as a groundbreaking intervention. Nevertheless, ethical considerations surrounding CRISPR technology and regulatory frameworks must be addressed to ensure responsible application and equitable access to this one-time gene editing therapy. As the authors celebrate this scientific advancement, sustained interdisciplinary collaboration and ethical scrutiny are essential to navigating the evolving landscape of CRISPR technology in medicine. This review aims to provide a detailed insight into the application of Casgevy, challenges associated with its application, future prospects of this therapy, and its comparison with existing treatment options for SCD.
镰状细胞病（SCD）是一种遗传性血红蛋白病，由β-珠蛋白链突变引起，该突变导致异常血红蛋白（HbS）聚合，并引发严重并发症。目前的治疗方案主要侧重于症状管理，治愈潜力有限。最近，Casgevy，首个用于治疗SCD的基于CRISPR/Cas9的基因疗法，已获得美国食品药品监督管理局（FDA）的突破性批准。临床试验表明，给12岁及以上的患者使用Casgevy能够对造血干细胞进行精确修饰，从而提高胎儿血红蛋白（HbF）水平，并显著减少血管闭塞性事件。与传统治疗方法不同，这种疗法提供了一种治愈方法，无需反复输血和移植，从而改善了SCD患者的生活质量。Casgevy已成为SCD患者的希望之光，由于其安全性、治愈潜力和变革性影响，标志着SCD管理可能发生范式转变，使其成为一种开创性的干预措施。然而，必须解决围绕CRISPR技术的伦理考量和监管框架，以确保负责任地应用这种一次性基因编辑疗法并实现公平获取。在作者庆祝这一科学进步的同时，持续的跨学科合作和伦理审查对于驾驭CRISPR技术在医学中不断发展的局面至关重要。这篇综述旨在详细介绍Casgevy的应用、其应用相关的挑战、该疗法的未来前景，以及它与SCD现有治疗方案的比较。
